Download The place of viruses in biology, a metabolism-versus-genes

The place of viruses in biology, a metabolism‐versus‐genes‐first debate
• Introduction: discovery, viral diversity and function
• Viruses and origin‐of‐life theorizing
• Revival of virocentric hypotheses
• The conceptual debate: are viruses alive?
• The phylogenetic debate: can viruses be placed in the tree of life? The discovery of viruses
~1900
1950
2000
time (years)
Dmitry Ivanovsky (1892)
Suspensions of plant tissues afflicted with mosaic tobacco disease infectious after
passage through ceramic filters retaining bacteria – leakage?
Martinus Beijerinck (1898)
Similar observation – interpretation: the infective agent (the "virus") was the liquid
Fiedrich Loeffler & Paul Frosch (1898)
Similar observation (infective filtrates) on the foot-and-mouth disease but retained
in filters of smaller grains –the causative agent: "filterable particles".
Viruses identified as extremely small infectious particles
Frederick Twort (1915) and Felix D'Hérelle (1917)
Viruses infecting bacteria: bacteriophages
What do we know about viruses?
Strict molecular parasites - depend on a cell to develop their reproductive cycle
Viral infective/reproductive cycle:
Viruses are extremely diverse
Viral classification according to:
• genetic material
enveloped
virus
capsid
Genetic
material
•
•
•
•
•
shape
capsid structure
envelope or not
additional structures (tail, appendices...)
hosts
Class
I - ds DNA
II - ssDNA
III - ds RNA
IV - ss RNA (+)
V - ss RNA (-)
VI - ss RNA with DNA intermediate (retroviruses)
VII - ds DNA with RNA intermediate
International Committee on Taxonomy of Viruses (ICTV - http://www.ictvonline.org)
Viruses are strict molecular parasites that "possess some of the properties of living systems such as
having a genome and being able to adapt to a changing environment"
Virus species is "a polythetic class of viruses that constitute a replicating lineage and occupy a
particular ecological niche”
2475 viral species, distributed in 395 genera, 22 subfamilies, 94 families and 6 orders
Viruses are important players in ecology
• Viruses are very abundant in nature (e.g. oceans)
Oceans
Suttle, Nat Rev Microbiol 2007
• Viruses are extraordinarily diverse: immense genetic reservoir
inferred from metagenomic studies (metaviromes – DNA, RNA)
Furhman, Nature (1999)
RNA viruses
Culley et al, Science 2006
Edwards & Rohwer, 2005
Viruses are important players in ecology
•
Abundant and diverse – significant fraction of biomass
•
Control population sizes (terminate blooms)
•
Biogeochemical cycles: nutrient cycling and sinking rates
•
Maintenance of biodiversity via 'kill-the-winner' strategies
Suttle 2007
Rodriguez-Valera et al, Nat Rev Microbiol 2009
Viruses are important players in evolution
• Models in population genetics to test evolutionary hypotheses
(high pop size + high number of generations per time unit)
• Foster evolution gene & genomes (high mutation & recombination rate)
• Selective pressure on populations (arms race)
• Horizontal gene transfer
& innovation in hosts
Viral-mediated HGT
• Through lysogenic cycles
• Recombination during infection
• CRISPR-mediated
Rohwer & Thurber, 2009
Amazing viruses...
Viruses from hyperthermophilic archaea
(D. Prangishvili)
Mimivirus and other Nucleo-Cytoplasmic
Large DNA Viruses (NCLDV)
Mimivirus, giant virus of amoeba
dsDNA virus
Raoult et al Science 2004
1.2 Mbp genome
>900 protein coding genes
several translation-related genes
sugar, lipid, aa metabolism
Mamavirus, 1.191 Mbp genome
Megavirus chilensis, 1.259 Mbp genome
... & the revival of an old debate
Viruses & origins of life
~1900
1950
2000
time (years)
Viral discovery simultaneous with conditions for a scientific investigation on the origin of life:
- Louis Pasteur (1860s): refutal of continuous spontaneous generation
- Charles Darwin (Origin of Species, 1859): species continuity to a common ancestor
- Immense progress in organic chemistry, biochemistry and cytology
Two opposed currents of thought – reflecting a chicken-egg dichotomy:
- Nucleocentric – self-replication
- Cytoplasmist – self-maintenance
Viruses:
- Mysterious nature
- Small size and infectivity
simplest living beings
"smallest = virus, smallest = first, so that virus = first"
Podolsky S. The role of the virus in origin-of-life theorizing. J Hist Biol 1996. 29:79-126.
1900
1950
1900 –1930
2000
time (years)
Nucleocentric (and virocentric!) models on the rise
• Leonard Troland
1914 – first life form was an "enzyme or organic catalyst"
1917 – "genetic enzyme"
• Hermann Müller
1922 – gene (Troland's "genetic enzyme") → gene = virus
1929 – first living organism was a primitive gene
• John B.S. Haldane (1929, The origin of life)
“life may have remained in the virus stage for many millions of years before a suitable
assemblage of elementary units was brought together in the first cell"
• Alexander & Bridges (1928) – living organisms divided in:
- Cytobionta (cells)
- Ultrabionta (viruses)
1944-1960: nucleocentric views raise again
1900
1950
2000
1930s & later
Cytoplasmist models on the rise
time (years)
• Alexander I. Oparin (1938, The origin of life – and later work)
life as a self-regulating system of catalytic reactions (metabolism first)
But also criticisms to the idea that simple = primitive
• Robert G. Green (1932)
• André Lwoff (1943, 1957): viruses as products of regressive evolution
• John B.S. Haldane (1932):
- "most evolutionary change has been degenerative"
- self-reproduction first but in a living system interdependence of genes & other components
• Avery et al. (1944): DNA as genetic material
• Herschey & Chase (1952): nucleic acid component of viruses is the infective element
• Watson & Crick (1953): DNA structure – self-copying mechanism
1900
1950
2000
time (years)
1960s to 2000s virocentric views abandoned
• Alexander I. Oparin (1961): viruses as products of cells
• Advances in biochemistry and molecular biology demonstrated that viruses are strict
molecular parasites – selfish genetic elements with an extracellular phase
• A better model for the origin of life: ribozymes and the "RNA world"
21st century: renaissance of old virocentric ideas
Proteins
• Very heterogeneous proposals with viruses being
central:
(catalysis)
- at operational level: seen functionally as living beings
- at phylogenetic level: viruses as descendants of viruses predating cells
Hammerhead ribozyme
Ribosome
RNA
(both)
DNA
(genetic
information)
Viruses as "inventors" of DNA and
donors of the DNA replication
system in the 3 domains
Viruses as integral domain of life
CEOs
Raoult & Forterre NRM 2008
REOs
Ultrabionta (viruses)
Cytobionta (cells)
Alexander & Bridges 1928
Giant viruses as 4th domain of life
(NCPLDV) Raoult et al Science 2004
"Ancient virus world"
and related models
"Viruses" predate
cellular life
Koonin et al. Biol Direct 2006
The conceptual debate: are viruses alive?
Defining life, a difficult task
"Metabolist" view
"Energy"
Self‐maintenance
"Geneticist" view
"Information"
Self‐replication and (darwinian) evolution
For metabolist views:
Viruses lack metabolism → viruses NOT alive ('borrowed life')
A conceptual trick: the virocell concept
virions
fish eggs


"virocell"
virus infecting a cell
"Virus factory", Claverie 2006
fish
"Virocell", Forterre 2012
Artifice to transfer the properties intrinsic to cells
(which viruses actually lack) to viruses
Epistemological "cheating"
Van Regenmortel 2010
Lopez-Garcia, Hist Phil Life Sci 2012
Moreira &and
Lopez-Garcia
2009
Lopez-Garcia & Moreira, Education, Evolution
Outreach 2012
The conceptual debate: are viruses alive?
"Metabolist" view
"Energy"
Self‐maintenance
For geneticist views:
"Geneticist" view
"Information"
Self‐replication and (darwinian) evolution
Viruses not able to self-replicate → NOT alive
Viruses do evolve but…
Two possibilities to consider viruses alive according to geneticist views:
1) Everything that evolves or is evolved is alive (includes viruses & "memes")
2) Extend the definition of virus to include a self-replicating capacity:
the virus world option, where virus has a dual meaning:
- contemporary viruses unable to self-replicate
- virus-like self-replicating entities (those that precede cellular life in this model)
CONFUSING, but acceptable
The phylogenetic debate:
can viruses be placed in the tree of life?
What is a tree of life?
Trees of organisms
versus
trees of genes
Paradox:
Forest of genes
for geneticist views (the only for which viruses could
be considered alive), a tree of life does not exist
network of genes
"core" gene trees
no tree of life
The phylogenetic debate:
can viruses be placed in the tree of life?
1) The virus world & related models
• Recognize the impossibility to place viruses in a tree of life
• No single gene shared by ALL viral families
•
Lack structural continuity
•
Genome volatility
• "Hallmark viral genes" largely distributed and/or protein folds absent from cells
• Structural motifs shared by capsid proteins from distant viral lineages &
infection of distant host by viruses of the same family: evidence for a common
origin predating cells?
Koonin et al 2006
Are some shared motifs proof of common & ancient origin?
?
(e.g. jelly-roll capsid protein)
Bamford et al 2005
Koonin et al 2006
Pranghishvili, Forterre & Garrett 2006
Alternative explanation 1: convergence
Simple geometrical protein structures → strong 3D constraints
Strong selection (imposed by structural or functional constraints)
→ high probability to converge to similar folds
Carboxysomes
Icosaedral virus
Alternative explanation 1: convergence
Convergence of complex structures: "eye"-bearing dinoflagellates
Erythropsidinium sp.
Family Warnowiaceae:
Phagotrophic unarmored
dinoflagellates with an ocelloid
•
Ocelloid:
Photoreceptor system with
cornea, lens and pigment cuplike structures (an "eye").
"Ontogenetically", it derives from
ancient chloroplast.
Warnowia sp.
Warnowia sp.
•
Erythropsidinium:
Also possesses a piston, an
extensible appendage (fragile)
•
Nematocysts
Extrusive organelles for prey
capture. Shared by some
warnowiids and some Polykrikos
Gomez et al., 2009
Alternative explanation 2:
Horizontal gene transfer (HGT)
HGT is extensive among viral lineages (likely cell mediated)
Some recent examples:
•
Multiple HGT events have occurred among dsRNA viruses from
different families
Liu et al. BMC Evol Biol 2012
•
Recombination events between RNA and DNA viruses (HGT)
Diemer & Stedman, Biol Direct 2012
Krupovic, BioEssays 2012
→ "Network-like rather than tree-like mode of viral evolution"
Koonin & Dolja, BMC Evol Biol 2012
Alternative explanation 3: host shifts
Can structural motifs shared by capsid proteins from distant
viral lineages & infection of distant host by viruses of the same
family be taken as proof of common and ancient origin?
NO!
Because alternative hypotheses cannot be discarded:
• Convergence !
• Host shifts !!
• Horizontal gene transfer !!!
NOT TESTABLE but valid as hypothesis
Pranghishvili, Forterre & Garrett 2006
D. Moreira & P. López-García (2009) Ten reasons to exclude viruses from the tree of life. Nat Rev Microbiol
Can viruses be placed in the tree of life?
2) Viruses (or some viral families) form a fourth domain in the tree of life
Genes shared by viruses and cells
Molecular phylogeny: need to compare homologous genes/proteins
TESTABLE
Cellular
organisms
Viruses
Common origin
Viral origin
HGT from hosts
Genes shared by viruses and cells: mostly cellular origin
Photosynthesis genes
Moreira, Mol. Microbiol. 2000
Williamson et al. PLoS ONE 2008
Do giant viruses form a fourth domain of life?
Concatenation of 7 proteins
?
(arg-tRNA-synthetase, met-tRNA-synthetase, tyr-tRNA-synthetase, RNA-pol-II large
subunit, RNA-pol-II second large subunit, PCNA, 5 ’-3 ’ exonuclease)
Mimivirus
Eukaryotes
Archaea
Human
Translation & other
informational genes
A. pernix
Yeast
A. thaliana
91
100
P. abyssi
100
100 98
A. fulgidus
100
0.2 substitutions/site
100
Bacteria
E. coli
B. subtilis
Mimivirus, giant virus of amoeba
Raoult et al Science 2004
M. tuberculosis
H0: Giant DNA viruses (NCLDV) constitute a
fourth domain of life
Potential problems of phylogenetic reconstruction
Long-branch attraction
(especially under simple
models of sequence evolution)
Poor sampling
(especially if genes from host missing!)
Do giant DNA viruses constitute a fourth domain of life?
NCLDV
nucleocytoplasmic large DNA viruses
Tyr-RS
Moreira & López-García 2005, Science
What about the rest of Mimivirus cell-like genes?
Giant viruses, giant chimeras
Moreira & Brochier-Armanet, BMC Evol Biol 2008
Eukaryotic origin 56%
Bacterial origin 29%
Archaeal origin 1%
Viral origin 5%
Unresolved 9%
Most viral cell-like genes have
been acquired by HGT from
host or bacteria (possibly
intracellular symbionts)
See also: Williams TA, Embley TM,Heinz E. Informational gene phylogenies do not support a fourth
domain of life for nucleocytoplasmic large DNA viruses. PLoS ONE 2011
Illustrative anecdotes…
Ten reasons to exclude viruses from the tree of life
Moreira & López-García Nat Rev Microbiol 2009
Clamp loader protein from Mimivirus (infecting amoeba)
and Ectocarpus silicosus ESV-1 (host: brown alga/Stramenopile)
Illustrative anecdotes…
Mimivirus forms a 4th domain of life
Raoult et al. 2004
2009
From a metabolist view…
…to a geneticist view
… to something fuzzy
("rhizome" of life)
Raoult 2010
In conclusion
• The epistemological discussion about whether viruses are alive or not
and whether some virus-like forms (using "virus" as a metaphor for selfreplicating entities) precede the first cells is a matter of debate that can
be understood within the metabolism-versus-genes dialectics
• Viruses cannot be included in the tree of life
For geneticists views a tree of life does not exist
For metabolist views – a tree of life exists but attempts to incorporate
viruses are artificial and alien to proper phylogenetic practice:
• Viruses do not share a common ancestry
• Viral recognizable cell-like genes have overwhelmingly been
acquired from hosts by horizontal gene transfer (HGT)
→ Consequently, the claim that viruses form a fourth domain in the tree of life
can be solidly refuted by proper molecular phylogenetic analyses and needs to
be removed from this debate
Lopez-Garcia, Hist Phil Life Sci 2012
Lopez-Garcia & Moreira, Education, Evolution and Outreach 2012
Thanks!
спасибо
David Moreira